Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
  • A61K35/66—Microorganisms or materials therefrom
  • A61K35/74—Bacteria
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
  • A61K35/66—Microorganisms or materials therefrom
  • A61K35/74—Bacteria
  • A61K35/741—Probiotics
  • A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/99—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
  • A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
  • A61Q19/06—Preparations for care of the skin for countering cellulitis
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/70—Biological properties of the composition as a whole
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
  • A61K47/38—Cellulose; Derivatives thereof

Definitions

• the present invention relates to a new composition for dermal administration of an active substance or principle.
• This composition can be a cosmetic composition, for example a slimming composition.
• active principles or active substances or substances is meant one or more active principles, whether medicinal or not. It may thus be, for example, a peptide or non-peptide compound, an extract of cells or tissues of animal or vegetable origin or a product obtained by fermentation of a microorganism, for example a bacteria or fungus.
• active principles or active substances or substances according to the definitions specified above will be used interchangeably.
• the invention relates to a composition for dermal administration, capable of forming a flexible film after drying on the skin as well as a matrix which can be used in such a composition.
• Dermal administration of active substances represents an interesting technique, endowed with certain advantages such as the absence of side effects. To be effective, this technique must, however, allow skin penetration over a prolonged period and sufficient to reach the targeted cells and obtain the desired effect.
• transdermal administration device commonly called "patch” consisting of a reservoir formed of synthetic plastic materials containing the active ingredient.
• This reservoir can be covered, on its face in contact with the skin, by a microporous membrane whose permeability to the active substance regulates its diffusion and consequently its dosage.
• other systems may be preferred to it. Indeed, it is known that the patch can peel off from the skin and, moreover, present an often unsightly appearance. Gels containing active substances have also been proposed.
• compositions of this type comprise an active principle, a polymer matrix forming a flexible film after drying, a solvent controlling the release of the active substance, namely a sorbitan macrogollaurate, a paraffin, a diglyceride or a medium chain fatty acid triglyceride or propylene carbonate as well as a solvent, for the matrix, capable of evaporating on the skin and finally a propellant making it possible to spray this composition contained in an appropriate device.
• a solvent controlling the release of the active substance namely a sorbitan macrogollaurate, a paraffin, a diglyceride or a medium chain fatty acid triglyceride or propylene carbonate as well as a solvent, for the matrix, capable of evaporating on the skin and finally a propellant making it possible to spray this composition contained in an appropriate device.
• compositions of patent EP 319555 by the presence of polymethacrylic derivatives, give off a characteristic odor which is quite unpleasant for the user and those around him.
• Other pharmaceutical compositions for topical administration containing an active principle, a solvent and various other ingredients are also known.
• a spreading agent such as isopropyl myristate or isopropyl palmitate
• compositions if they can be used for topical dermatological applications, prove to be completely unsuitable for application by spraying even after adding 10 to 40% of a propellant gas as recommended, because they appear too viscous and likely to have various disadvantages such as blockage of the spray device.
• patent EP 289900 which relates to antibacterial compositions for topical use comprising:
• a physiologically acceptable non-aqueous solvent capable of dissolving the release matrix, the active principle and the transcutaneous absorption promoter as well as being rapidly eliminated by evaporation in contact with the skin, intended, after administration of the medicinal substance, to provoke a preventive or therapeutic response.
• the drug particularly used in this patent application is Pestradiol. The search for a composition allowing the diffusion through the dermis of active substances, from a small covering surface and at rates compatible with a treatment while being free from the drawbacks previously reported remains of major interest.
• compositions more particularly cosmetic compositions for dermal administration, from a film formed on the skin, which are devoid of the drawbacks mentioned above but capable, from a reduced and controllable overlap area, of delivering the active substance in a regular, continuous manner and at rates largely reaching the possibility of achieving the desired effect.
• a cosmetic composition for dermal administration comprising:
• a non-aqueous solvent capable of dissolving the release matrix, the active principle and the skin absorption promoter as well as being rapidly eliminated by evaporation on contact with the skin, 5) at least one propellant gas.
• the polymer matrix is generally chosen from polymeric or copolymeric substances capable of both forming a flexible film after evaporation of the solvent and of releasing the active substance.
• This matrix is formed in the stratum corneum after evaporation of the solvent capable of releasing the active substances.
• this matrix is present in an amount of 0% to 7% of the weight of the composition according to the invention, for example from 4% to 7%, for example 3%.
• 1% to 5% by weight of matrix, in particular 3% is used.
• the choice of this matrix will mainly relate to polymeric or copolymeric substances soluble in the physiologically acceptable solvent so as to form a homogeneous solution.
• cellulose polymers or copolymers capable of meeting the above criteria, more particularly retained are cellulose polymers or copolymers, in particular because after drying they represent an appropriate abrasion resistance and mechanical stability. For this reason, cellulosic matrices of this type can be brought into contact with water without fear of deterioration.
• Ethylcellulose represents the preferred cellulosic polymer and, therefore, the release matrix of choice for the formation of a flexible film in contact with the skin.
• the polymer matrix can consist of a vinylpyrrolidone / vinyl acetate copolymer such as polyvinylpyrrolidone / vinyl acetate, hereinafter referred to as PVPVA.
• PVPVA polyvinylpyrrolidone / vinyl acetate
• the subject of the invention is a cosmetic composition for dermal administration comprising:
• a salting-out polymer matrix capable of forming a flexible film after drying chosen from cellulosic polymers or copolymers or vinylpyrolidone / vinyl acetate copolymers,
• the active substance for its part, will be chosen from substances soluble in the solvent and capable of continuously crossing the epidermis and / or the dermis with a sufficient flux to give an effective concentration from a cutaneous area of dimension reduced but sufficient.
• compositions of the invention will be incorporated into the compositions of the invention at a rate, in particular from 0.1 to 20% of the weight of these compositions, it being understood that each active substance will be introduced at individualized concentrations known in the art for dermal administration. or adapted to this route of administration.
• the polymer matrix and the active principle are combined with a skin absorption promoter.
• the latter enters into the compositions of the invention advantageously at a rate of 15 to 30% by weight of this composition, preferably from 15 to 25%, for example 20%.
• This absorption promoter is chosen in such a way that it can bring about significant dermal flows in order to obtain the desired effects by means of an acceptable skin covering, that is to say less than 150 cm 2 but preferably between 10 and 40 cm 2 for example 30 cm 2 .
• the skin absorption promoter in question must be capable of temporarily disorganizing the skin barrier so as to increase the permeability of the skin without irritating it while promoting the diffusion of the active principle chosen according to kinetics and sufficient concentration that can be maintained for a period of time.
• This skin absorption promoter will be selected from compatible substances in the non-aqueous solvent capable of evaporating rapidly on contact with the skin.
• it will be chosen from the following compounds which have the necessary degree of solubility in the physiological solvent in question and which combine the best qualities reported above, that is to say:
• esters of aliphatic fatty acids essentially esters having in total from 10 to 30 carbon atoms optionally substituted by one or two hydroxyl, carboxylic or acyloxy groups at dC 4 such as acetoxy, or optionally interrupted by one or two bonds ethylenic or by one or two ether oxygen
• aliphatic fatty alcohols essentially C 10 -C 3 alcohols optionally substituted by one or two hydroxyl, carboxylic or acyloxy groups at dC 4 such as acetoxy or optionally interrupted by one or two ethylenic bonds or by one or two oxygen ether.
• Particularly preferred absorption promoters which can be selected from the esters of aliphatic fatty acids and aliphatic fatty alcohols mentioned above are reported below, namely: a) esters of aliphatic fatty acids of general formula:
• R represents a C 2 -C 7 linear or branched alkyl or alkenyl group optionally substituted by a CC 4 hydroxyl, carboxylic or acyloxy group and R 1 represents a linear or branched C 3 -C 8 alkyl group optionally substituted by one or two hydroxyl groups such as for example an isopropyl, 2-ethyl-dihydroxyethyl group or R ⁇ represents a group -CH 2 -CH 2 -O- (CH 2 ) 2 -O-CH 2 -CH 3 , the aliphatic fatty acid ester comprising a minimum of 10 carbon atoms and a maximum of 2 hydroxyl groups.
• This compound is marketed under the name Dragoxat® and is also called octyloctanoate.
• the non-aqueous solvent capable of dissolving the release matrix, the active principle and the skin absorption promoter, it will be chosen from compounds with a relatively low boiling point, namely below 100 ° C. at atmospheric pressure, so that it can be quickly eliminated by evaporation on contact with the skin and likewise help the formation of a film by drying without, however, causing local irritation.
• Such solvents are generally used in an amount of 44 to 84.9% by weight of the final composition and can be selected from volatile compounds such as dichloromethane, ethanol, isopropanol or ethyl acetate. Ethanol and isopropanol are the solvents of choice. However, ethanol represents a preferred solvent according to the invention since it contributes effectively to the formation of films on the skin while evaporating rapidly on contact with the skin.
• the propellants usable according to the invention are chosen from: butane propane isobutane carbon dioxide dimethyl ether hydrochlorofluorocarbon hydrofluorocarbon nitrogen isopentane nitrogen oxide pentane Butane or propane is preferred
• the invention relates to a cosmetic composition
• a cosmetic composition comprising:
• a polymeric release matrix capable of forming a flexible film after drying chosen in particular from cellulose polymers or copolymers such as ethylcellulose.
• a cutaneous absorption promoter of the active principle in particular from 15% to 25% of a fatty acid ester or of a fatty alcohol chosen from: 2-ethylhexanoate 2-ethylhexyl isopropyl myristate myethylate of diethylene glycol monoethyl ether isopropyl palmitate 2-octyldecanol 2-ethylhexyl undecylenate 2-ethylhexyl succinate 12-hydroxystearear 2-ethylhexyl 2-ethylhexyl acetoxystearate glycerol isostearate hexyl laurate 4) from 44% to 84.9% of a non-aqueous solvent capable of dissolving the release matrix, the active principle and the skin absorption promoter as well than to be rapidly eliminated by evaporation on contact with the skin, in particular ethanol or isopropanol
• a sprayable composition has been more particularly tested to be applied in a metered spray bottle, cosmetically satisfactory, and whose application surface and dose characteristics are controlled and reproducible.
• the active substances used can be intended for the production of a film for targeting, for example a slimming film.
• the film according to the present invention relates to a cosmetic composition containing slimming substances.
• This slimming substance may be a neuropeptide Y receptor antagonist.
• the neuropeptide Y hereinafter briefly designated "NPY” is a neuromediator which is involved in a number of physiological processes and for which an implication in the regulation of lipolysis has been demonstrated (P.Valet. J. Clin. Invest. 1990, 85, 291-295). It has been described in EP 838217 that the NP Y-antagonists can be used for the preparation of cosmetic compositions.
• compositions containing an NPY-antagonist component can be used as regulators of lipoiysis / lipogenesis in the skin without interfering with the natural functions thereof. It has also been described that cosmetic slimming compositions containing an NPY-antagonist component and an ⁇ 2-antagonist component are particularly advantageous.
• the present invention relates to a film containing a slimming cosmetic composition containing at least one NPY-antagonist component with another active substance such as an oc2-antagonist.
• the NPY-antagonist contained in the cosmetic composition can be a non-peptide compound, a peptide, an extract of cells or tissues of animal or vegetable origin or a product obtained by fermentation of a microorganism, for example of a bacteria or fungus.
• These components are also non-peptide synthetic compounds, peptides or products obtained by fermentation of a microorganism, for example a bacterium or a fungus or by extraction of cells or tissues of animal origin. or vegetable.
• the deposited film of course needs to be well tolerated but also to have an attractive cosmetic appearance with rapid evaporation of the vehicles, leaving little residue on the surface of the skin.
• the cosmetic evaluation of a series of formulations applied in film to the skin has been carried out.
• the objective was to characterize all of the cosmetic properties of the solutions to be sprayed using a sensory analysis study.
• This is a sensory study according to six criteria identified as being appropriate (the conduct of the protocols and the type of calculation adopted correspond to the AFNOR standards published for the food industry). These criteria are as follows:
• the formulation is sprayed onto the skin at a measured distance of 10 cm. Observations begin 10 minutes after application, this duration is standardized for sensory analysis protocols. One spray corresponds to 130 ⁇ l of formulation on an area of approximately 35 to 40 cm 2 .
• the excipients used are:
• film-forming agent ethylcellulose 99 N7NF (7 mPa.s.: Aqualon)
• the average values obtained for the ten experimenters are accompanied by high and low values.
• the evaluation of the formulations is detailed here with respect to the reference formulation (R) by highlighting the changes in composition which affect or improve its cosmetic appearance.
• Table B summarizes the main interpretations concerning the influence of the different excipients compared to the reference formulation.
• the perception of the reference formulation (R) is improved by limiting the amount of ethylcellulose to 3% (A) (less fatty, less sticky and less residue).
• An improved spraying capacity is thus obtained by better dispersion of the formulation by the device pump.
• This 3% it is even possible to increase the incorporated Dragoxat® to 30% while keeping a very good perception of the sprayed formulation (C).
• the formulation which is classified immediately after (E) has a slightly larger residue. It still contains 3% ethylcellulose but the solvent contains an isopropanol fraction which is more difficult to spray.
• the reference formulation is a bit greasy and sticky. By limiting only the amount of ethylcellulose from 0.5 to 3% the results are much improved and satisfactory.
• the residue is weak to very weak, rather shiny but not greasy and not very sticky. Penetration is fairly rapid to very rapid. More particularly, according to the invention, a formulation of films containing slimming active agents has been developed.
• slimming active agents are preferably antagonists of the neuropeptide Y receptors (NPY) or antagonists of the ⁇ 2 receptors. A large number of them are described in patent application EP 838217.
• the cutaneous absorption of an active principle is akin to passive diffusion, the limiting stage being at the time of crossing the stratum corneum, 1,000 times more impermeable than epidermis or dermis.
• One of the main advantages expected from the films according to the invention is to remove this cutaneous resistance to diffusion. This increase in skin absorption is the result of an increase in hydration and temperature of the stratum corneum, following the semi-occlusion of the application site, caused by the film.
• the expected benefits of slimming films are primarily aimed at body areas characterized by the presence of resistant cellulite.
• the advantageous aspect of the films results on the one hand from the structure of the matrix containing the active substances, and on the other hand from its application system. Being directly sprayable on the skin, the film forms a thin, flexible and invisible film, from which the active substances are diffused.
• the small thickness of the film formed makes it possible not to disturb the gaseous and aqueous exchanges existing between the skin and the external medium, thereby improving the tolerance of the product.
• the flexibility of the film also offers better comfort.
• the film contains antagonistic NPY and ⁇ 2 antagonistic active agents, in a concentration 10 times greater than that retained in the conventional fluid as described in EP 838217.
• the film makes it possible to saturate the adipocyte storage receptors effectively and durably by the antagonists. of the NPY receptor and of the ⁇ 2 receptor, leading to a reduction in areas traditionally resistant to slimming treatments.
• compositions according to the invention for dermal administration can be prepared, in a conventional manner, by a person skilled in the art, by mixing the various constituents in the chosen proportions. For example, it is possible, with stirring, to dissolve the skin absorption promoter in the solvent and then add the active principle and finally the release matrix. All of the substances included in the compositions of the invention constitute known products or can be prepared by known methods, some of these products being commercially available.
• the dermal compositions of the invention thus obtained can be applied by any means to a skin area for example to an area between 10 and 40 cm 2 for example 30 cm 2 in particular and preferably by direct spraying using a metering pump of known type and marketed with the aid of a propellant such as a compressed or liquefied gas.
• compositions of the invention can thus be administered by spraying from a container fitted with a metering valve, containing in addition a propellant gas such as nitrogen or nitrous oxide, or liquefied gas such as butane or propane.
• a propellant gas such as nitrogen or nitrous oxide, or liquefied gas such as butane or propane.
• the invention relates to a matrix intended for cosmetic compositions for the dermal administration comprising: a) a polymeric matrix, for the release of an active principle, capable of forming a flexible film after drying b) a promoter of skin absorption of an active ingredient c) a non-aqueous solvent capable of dissolving the release matrix and the skin absorption promoter as well as being rapidly eliminated by evaporation on contact with the skin d) a propellant
• the polymer matrix will be selected from polymeric or copolymeric substances, in particular from cellulosic polymers or copolymers as explained above, while the cutaneous absorption promoter will appear from esters of aliphatic fatty acids or aliphatic fatty alcohols as described. previously in particular esters of formula I or alcohols of formula ⁇ .
• the non-aqueous solvent is a compound with a boiling point below
• the release matrix represents from 0% to 7%
• the skin absorption promoter represents from 15% to 30%
• the nonaqueous solvent represents from 44% to 84.9%, these percentages being expressed by weight of the final cosmetic composition.
• These matrices for dermal compositions according to the invention can be prepared, in a conventional manner, by mixing, in the chosen proportions, the various ingredients which constitute them.
• the propellants are advantageously chosen from propanol or butanol.
• the film-forming compositions of the invention as well as the matrices for dermal compositions according to the invention have indisputable advantages since they are capable of causing the cutaneous diffusion of an active substance, so as to produce constant and controlled effective rates over a period of time. prolonged period of at least 12 hours from a skin covering area of the order of 10 to
• compositions and matrices for dermal compositions according to the invention while being devoid of any unpleasant odor, spread out in a homogeneous film over the entire selected skin area.
• compositions of the invention in the form of a flexible film, provide better comfort for the user and, thanks to their transparency, are completely invisible.
• the cosmetic compositions according to the invention preferably contain slimming active substances.
• the slimming active substances are preferably chosen from NPY or ⁇ 2 receptor antagonists.
• the active substances used are in this case for example the extracts of strain
• Streptomyces sp SEBR 2794 registered with the C.N.C.M. from the Institut Pasteur under number 1-1332, and extracts of the Bacillus licheniformis SEBR 2464 strain, deposited with the C.N.C.M. of the Institut Pasteur under the number 1-1778. They will be called hereafter slimming active substance.
• a clinical efficacy study was carried out with a slimming composition containing NPY and ⁇ 2 receptor antagonists. The purpose of this study was to assess the effectiveness of the film in use coupled with the Lipofactor® fluid.
• Protocol The test is carried out over a period of 28 days and involves 31 women. The inclusion of subjects was carried out after a clinical examination and verification of the presence of areas of anchored cellulite. The subjects apply the fluid and the film on the same leg, defined randomly, the contralateral leg being taken as an untreated control. The fluid is applied at discretion on the entire thigh, from the knee to the gluteal fold.
• the application is carried out in the evening without massage apart from that necessary for the penetration of the product.
• the film is applied in the morning in a very localized manner on the following 4 sites:
• the amount of film used per day corresponds to two sprays juxtaposed so as to cover the area concerned.
• the evaluation of the effectiveness is carried out at To (before treatment) and at T28 days and uses three different methods:
• Table 2 Average decreases in adipose tissue depending on the sites treated
• the clinical assessment of the macro-relief is carried out using photographic images by five assessors. After random distribution, all the photographs are scored by the assessors by comparison to a standard range (reference photographs), structured around 7 intensity grades.
• the images of the external faces of the treated thighs and controls of the 31 volunteers made it possible to clinically confirm, after analysis by the 5 evaluators, an improvement in skin relief.
• the film is applied for 4 weeks at the rate of two juxtaposed sprays so as to cover the area concerned.
• the effectiveness of the film is evaluated at the end of the study.
• Propellant gas by mixing for 30 seconds and with magnetic stirring 73 g of ethanol and 20 g of 2-ethylhexyl 2-ethylhexanoate. 2 g of active slimming substance (s) are then added, in small portions, to the mixture obtained, then, after complete dissolution (5 minutes), 5 g of 6mPa.sec ethylcellulose are introduced, with vigorous stirring. , in order to avoid the formation of lumps. The final solution obtained is slightly opalescent, homogeneous.
• aluminum boxes are filled with 5 ml of the previously obtained solution and they are fitted with a crimped pump pump comprising a push button. The pump is activated twice to prime before its first use.
• 98 g of a dermal matrix are prepared by mixing, for 30 seconds, 73 g of ethanol and 20 g of 2-ethylhexyl 2-ethylhexanoate. 5 g of ethylcellulose 6 mPa.sec are then added, with vigorous stirring, in order to avoid the formation of lumps.
• the matrix thus obtained is ready to receive an active, by incorporation, so as to form a cosmetic composition containing 2% by weight of this active, applicable by spraying.
• Reminder of the reference formulation 95 ° ethanol: 75%; Dragoxat®: 20%; ethylcellulose: 5%.
• Table B Classification of the evaluation of excipients compared to the reference formulation

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• 1998
  • 1998-12-24 FR FR9816422A patent/FR2787712B1/fr not_active Expired - Fee Related
• 1999
  • 1999-12-08 JP JP2000590612A patent/JP2002533383A/ja not_active Withdrawn
  • 1999-12-08 CA CA002350685A patent/CA2350685A1/en not_active Abandoned
  • 1999-12-08 HU HU0200095A patent/HUP0200095A2/hu unknown
  • 1999-12-08 AU AU45205/00A patent/AU4520500A/en not_active Abandoned
  • 1999-12-08 EP EP99973534A patent/EP1140040A1/fr not_active Withdrawn
  • 1999-12-08 IL IL14314499A patent/IL143144A0/xx unknown
  • 1999-12-08 PL PL99365376A patent/PL365376A1/xx not_active Application Discontinuation
  • 1999-12-08 WO PCT/FR1999/003051 patent/WO2000038658A1/fr not_active Application Discontinuation
  • 1999-12-08 KR KR1020017008101A patent/KR20010089699A/ko not_active Application Discontinuation
  • 1999-12-08 TR TR2001/01569T patent/TR200101569T2/xx unknown
  • 1999-12-08 BR BR9916814-6A patent/BR9916814A/pt not_active Application Discontinuation
  • 1999-12-08 CN CN99814967A patent/CN1331587A/zh active Pending
• 2001
  • 2001-06-21 NO NO20013117A patent/NO20013117L/no not_active Application Discontinuation

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